FAQ

General Questions

Why is there a need for PGENI?

The reliance on FDA and EMEA safety and dosing data needs to be given local context for each country. It would be unethical and irresponsible to not use the bountiful pharmacogenetic information now. More refined data and broadly applicable technologies will come in the future, but that should not obstruct progress for today.

Is there really enough variation between populations to support a meaningful analysis?

Yes. Significant data exists in the scientific literature for DNA changes that are predictive for risk of toxicity or lack of effectiveness for commonly used medications.

How does PGENI determine what variants to look at?

Similar to the identification of the key genes to be screened by PGENI, the scientific literature was screened for DNA variations in each gene that have an effect on the drug outcome.

Why hasn’t the PGENI approach been tried in the past?

Only now has the critical mass of data and efficiency of technology enabled this approach to be undertaken at such a broad scale.

What is PGENI?

PGENI is the *P*harmaco*g*enetics for *E*very *N*ation *I*nitiative.

Participants

Why is PGENI specifically looking at developing countries?

Pharmacogenetics is already becoming a part of the health care environment for wealthy countries. PGENI can and will work with many developed countries. However, PGENI feels that there is an opportunity to transform the practical utility of genetics, through more enlightened drug selection in developing nations.

How was the PGENI country list selected?

Selection was based on two factors:
1) WHO (World Health Organization) ranking of gross healthcare expenditure
2) Total population of countries with a population of > 200,000 were included. The top 40 and bottom 40 countries were then excluded from the list.

What is PGENI looking for in individual countries?

PGENI has identified common ethnic groups that are categorized as the major ethnic groups (>9.9%) within each country. PGENI is asking for 500 blood samples (250 male and 250 female healthy volunteers) from each ethnic group.

How was this ethnic information collected?

Ethnic information was collected from Microsoft Encarta, US Department of State, CIA World Fact Book, and individual country governmental websites.

Pharmacogenetics

What is pharmacogenetics?

Pharmacogenetics is the study of inherited variability to drug response. Different people react differently to medicine. Pharmacogenetics identifies the differences in each persons genetic makeup that could cause different reactions to drugs.

Why do we care about pharmacogenetics?

Pharmacogenetics could explain why some people have adverse reactions to medications while others who take the same medication have a complete response. Pharmacogenetics could heavily influence therapy selection in the future. For more information about pharmacogenetics click here.

Medication Utilization

What is the current strategy for therapy selection?

Drugs are primarily developed in white European derived patients (US, UK, Australia/New Zealand). The safety and efficacy data is then used by the rest of the world as guidance for drug administration.

How successful is the current strategy for therapy selection?

For most drugs, current therapy selection is only successful in controlling the disease or symptoms of interest in less than 50% of the patients.

PGENI Study Logistics

What drugs are going to be looked at?

The PGENI drug list was derived from the 14th Essential Medicines list published by the WHO (World Health Organization). The list was annotated to focus on systemic (medicines taken orally or by injection) medications only and those that were most likely to be available and used in developing nations. PGENI hopes to incorporate all medications in the future.

How does PGENI determine what genes to look at?

Using the WHO Essential Medicines List, PGENI looked through over 400,000 publicly available abstracts to identify genes involved in the metabolism, transport and the targets of every PGENI drug. The resulting “essential genes” list provides the basis for the initial PGENI analysis.

How does PGENI determine what variants to look at?

Similar to the identification of the key genes to be screened by PGENI, the scientific literature was screened for DNA variations in each gene that have an effect on the drug outcome.

What is PGENI looking for in these samples?

PGENI will use the samples solely to evaluate genetic information for variants of interest that could generate recommendations for medication selection in a particular country.

What kind of information is collected or stored regarding these blood samples?

PGENI will only collect and store information on age, gender and ethnicity/racial affiliation for each particular blood sample. No other information will be collected or stored.

How is PGENI structured?

PGENI has an executive council with a coordinating center and regional pharmacogenetic centers. The coordinating center and regional centers support the efforts in each PGENI country.

How will PGENI look for variation between populations?

By collecting the frequency of pharmacogenetic markers (genotyping) in the major ethnic groups within each PGENI country. Information on the frequency of markers for poor drug response or toxicity will allow selection of alternate medications in “at risk” populations.

Will there be monitoring of ethical considerations of PGENI?

PGENI has received approval by the Washington University Human Studies Committee and the University of North Carolina IRB. Ethical reviews will also be conducted within each nation participating in PGENI. PGENI will also conduct ethics research, to further develop and refine the ethical conduct of genetics research throughout the world.

What type of output will PGENI produce?

PGENI will have 2 types of output: surveillance and prioritization. PGENI will identify population subgroups at high risk of toxicity or treatment failure based on genetic information in order to enhance patient surveillance or monitoring. PGENI will also assist in treatment selection from among the WHO recommended therapies by identifying population risk signals.